Professor Receives $1.6 Million to Study Potential Hepatitis C Drugs

A University of Mississippi pharmacognosy professor has been awarded a $1.6 million research project grant from the National Institutes of Health to conduct studies on potential drugs for hepatitis C.

"There is a significant need for new drugs to treat hepatitis C," says Mark T. Hamann, principal investigator on the project. "Based on recent data suggesting that endophytes are actively involved in the biosynthesis of established drugs, we are focusing on the bacteria and fungi that live inside the tissues of plants."

Endophytes have a surprising ability to produce drug or druglike molecules, Hamann says.

"We will explore various endophytes and develop better ways to culture or grow them," he says. "Culture is a challenge because they are difficult to grow outside of their host plant. After we grow the bacteria and fungi, we will assess their ability to produce potential drugs for hepatitis C and their response to various forms of stimuli."

Only four drugs are available to treat the disease.

"Hepatitis C is an emerging infectious disease with an increasing patient population," Hamann says. "The risk associated with the disease is developing liver cancer, so there is a great need to develop effective treatments."

When Hamann first learned that he had received the grant, he immediately credited students and collaborators who helped assemble the proposal.

"My students and longtime colleagues Tony Whitaker, director of biology at RSS Pharma LLC in Atlanta, and Raymond Schinazi, director of the laboratory of biochemical pharmacology at Emory University, did a great deal of the heavy lifting," he says. "They were instrumental in gathering preliminary data for the proposal and helping to prepare various aspects of the program."

Hamann's students are conducting individual projects related to the overall research goal. Vedanjali Gogineni, a visiting scholar who plans to pursue a doctorate under Hamann, has been working on the purification and characterization of new natural products. Graduate students Amanda Waters, Joonseok Oh and Christopher James also are contributing to the research.

Waters, who received a National Science Foundation predoctoral fellowship earlier this year, is developing better methods and tools for characterizing complex natural products generated from microbes.

James and pharmacy honors student Kelli Dulaney have been working with Xylella fastidiosa, a type of bacteria that can kill grapes, citrus plants and hardwoods. The bacterium, which has been an enormous problem for the American wine industry, acts as a pathogen in many ways but also lives inside healthy plants, making it a noteworthy subject of study.

"The endophyte generates (not only) new metabolites that remain to be characterized but also well-established drugs that were once thought to be generated only by soil bacteria," Hamann says. "Christopher and Kelli's data strongly suggest that endophytes may be a unique group of drug- producing organisms that will yield some interesting treatments in the future."

Oh is studying the fruits of several endangered species with the help of Ted Leininger, a plant pathologist with the U.S. Forest Service. One such species is Lindera melissifolia, a shrublike plant commonly known as pondberry.

"The pondberry has a wonderful fragrance that we extracted using a very basic method," Oh says. "We tested to see if the essential oil has any interesting and discovered that the plant has some tick- and insect-repellant properties. This is an example in which a plant-derived insect repellant useful in the control of Lyme disease and malaria may be produced by an endophyte."

Recent graduates contributing to the success of Hamann's project include Bin Wang, a postdoctoral fellow in the University of Oklahoma's Department of Chemistry; Sam Abbas, a medical student at the UM Medical Center in Jackson; and John Bowling, a postdoctoral research fellow at St. Jude Children's Research Hospital in Memphis.

Hamann is looking forward to working with these and other graduate students on the project. "I enjoy working with graduate students," he says. "They bring a great deal of energy and enthusiasm to the program."

Although their primary goal is to investigate endophytes as a source for new inhibitors of hepatitis C, the team is also assessing their bacterial extracts against a broad suite of targets associated with infectious diseases, cancer and neurodegeneration.